16  ON   GERMINAL   TRANSPLANTATION   IN   VERTEBRATES. 

tail."  This  is  such  a  result  as  we  should  expect  had  the  hen  not  been  oper- 
ated upon  at  all.  It  is  fully  accounted  for  if  we  assume  that  the  ova  which 
produced  these  twelve  chicks  came  from  regenerated  ovarian  tissue  of  the 
white  mother  herself.  On  the  other  hand,  if  the  transplanted  ovary  had 
produced  the  chicks  without  any  foster-mother  influence,  the  chicks  should 
have  been  all  black  with  light  ventral  surfaces,  which  they  were  not.  Again 
the  regeneration  hypothesis  presents  far  less  difficulty  than  that  of  a  suc- 
cessful transplantation. 

SERIES  II.     ROOSTER  WHITE. 

White  hen  W 1  control,  mated  with  the  w]jite  rooster,  had  eighteen  chicks 
"pure  white  to  light  buff  when  hatched."  White  hen  W2  and  black  hen 
B  2  had  their  ovaries  exchanged,  and  were  later  bred  to  the  white  rooster. 

Black  hen  B  2  produced  nine  white  chicks  and  11  white  spotted  sparingly 
with  black.  Such  a  result  as  this  is  the  usual  consequence  of  a  cross 
between  black  fowls  and  white  ones;  that  is,  it  is  what  might  have  been 
expected  had  the  black  hen  never  been  operated  upon.  And,  on  the  other 
hand,  if  the  functional  ova  came  from  the  transplanted  ovary,  the  expectation 
would  not  be  materially  different,  though  the  breeding  capacity  of  the  young 
would  be  different  in  the  two  cases.  Unfortunately  this  was  not  tested. 

The  white  hen  W2,  which  had  received  the  black  ovary  from  B  2,  pro- 
duced five  chicks.  Three  were  white,  one  white  spotted  with  black,  and 
one  black.  A  white  hen  not  operated  upon  might  be  capable  of  producing 
all  three  sorts  when  mated  with  a  white  rooster  of  a  similar  character; 
that  is,  both  parents  might  be  Mendelian  heterozygotes  bearing  black  as 
a  recessive  character,  in  which  case  one-quarter  of  the  young  should  be 
black.  Now,  the  numerical  result  is  not  at  variance  with  such  an  interpre- 
tation. But  if  the  same  white  rooster  was  used  in  this  mating  as  with  B  2, 
it  is  surprising  that  no  black  young  were  produced  by  B  2 .  Guthrie  does 
not  expressly  state  that  the  same  rooster  was  used  in  both  cases,  but  we 
assume  this  to  have  been  the  case  from  his  use  of  the  expression  ''the  white 
rooster. ' '  If  different  males  were  used  in  the  two  cases,  one  may  well  have 
been  homozygous,  the  other  heterozygous.  In  that  case  the  black  chick 
as  well  as  the  white  and  the  spotted  ones  may  have  come  from  regenerated, 
not  from  transplanted  tissue.  But  if  the  same  white  rooster  was  used  in 
both  cases,  it  is  still  equally  difficult  to  account  for  the  black  chick  as  a 
product  of  a  transplanted  germ-cell  or  of  regenerated  ovarian  tissue  of  the 
white  mother.  For  unless  the  white  male  was  heterozygous  in  black  we 
should  expect  no  black  young  to  be  produced  even  were  every  egg  which  he 
fertilized  produced  by  a  pure-black  hen,  instead  of  by  a  white  hen  possibly 
carrying  borrowed  black  germ-cells. 

Control  matings  of  the  white  rooster  with  normal  black  hens,  or  of  the 
black  chick  when  it  became  adult,  would  have  cleared  up  the  case,  but  no 
control  crosses  were  made  by  Guthrie.  The  control  mating  of  "the  white 
rooster* '  with  a  normal  white  hen  W 1  was  not  a  sufficient  control  of  his 


EXAMINATION   OF  OBSERVATIONS   OF   GUTHRIE  AND   MAGNUS.  17 

breeding-  capacity.  It  does  not  prove  him  to  have  been  homozygous  in 
white.  If  W 1  was  homozygous,  only  white  chicks  would  be  expected,  what- 
ever the  character  of  the  white  rooster. 

We  have  now  examined  in  detail  the  two  pairs  of  transplantation  exper- 
iments which  form  the  entire  basis  of  Guthrie 'e  assumption  that  the  foster- 
mother  may  in  a  case  of  homoplastic  transplantation  affect  the  character  of 
the  offspring-.  In  no  one  of  the  four  cases  does  the  hypothesis  that  the 
transplanted  ovary  functioned  offer  less  difficulty  than  the  hypothesis  that 
only  regenerated  ovarian  tissue  functioned.  In  two  of  the  four  cases  the 
advantage  is  overwhelmingly  with  the  latter  hypothesis.  That  ovarian 
tissue  mig-ht  easily  be  left  behind  in  exchanging-  ovaries  between  two  ani- 
mals Guthrie  frankly  admits  in  a  recent  paper  (1910),  citing  experiences 
of  his  own  to  show  just  how  this  might  come  about.  He  still  maintains, 
however,  his  belief  in  foster-mother  influence,  because,  we  believe,  of  a  fail- 
ure to  grasp  fully  the  laws  of  inheritance  of  the  character  which  he  used  as 
a  criterion.  A  similar  failure  is  shown  by  the  comment  which  he  makes 
in  Science  (1909)  upon  the  case  which  we  have  more  fully  described  in  this 
paper  (Group  I) .  Referring  to  our  failure  to  detect  foster-mother  influence 
in  the  young  borne  by  female  27,  he  says  :  "Had  the  operated  pig  been 
bred  to  a  male  of  the  same  strain  as  the  pig  from  which  the  engrafted  ovary 
was  obtained  *  *  *  characteristics  in  the  offspring  indicative  of  such 
influence  might  have  been  obtained."  Now,  suppose  the  operated  pig  had 
been  so  bred,  what  result  might  have  been  expected?  Exactly  that  which 
was  obtained  from  the  mating  with  an  albino,  only  we  should  have  been  left 
in  uncertainty,  precisely  as  in  Guthrie 's  own  experiments,  as  to  whether 
the  pigmentation  of  the  offspring  was  due  to  maternal  or  paternal  influence. 
By  the  mating  with  an  albino  male  all  such  uncertainty  was  eliminated, 
since  it  was  rendered  sure  that  if  the  offspring  were  pigmented  they  could 
have  derived  this  character  from  no  other  source  than  the  transplanted 
ovary  of  the  little  black  guinea-pig. 

Our  case  does  not  prove  that  foster-mother  influence  is  impossible.  No 
such  claim  is  made  for  it.  But  our  observations  do  show  that  evidence  such 
as  Guthrie  has  presented  is  wholly  without  value  in  establishing  foster- 
mother  influence,  and  that  in  one  specific  case,  the  first  critical  case  on  rec- 
ord, we  believe,  no  foster-mother  influence  is  detectable. 

In  view  of  our  own  experiments  on  guinea-pigs,  in  which  the  source  of 
the  tissue  which  liberated  the  ova  is  fully  established  and  in  which  no  foster- 
mother  influence  is  detectable,  we  may  fairly  ask  that  the  experiments  with 
fowls  be  repeated  on  adequately  controlled  material  before  we  accept  the 
interpretation  which  Guthrie  has  given  to  his  results.* 

*While  this  paper  was  in  press  our  attention  was  called  to  the  fact  that  Dr.  C.  B. 
Davenport  (1910,  Proc.  Soc.  Exp.  Biol.Med.,  vol.  vn,  p.  168)  had  indeed  repeated  Guth- 
rie's  experiment  with  fowls,  on  material  adequately  controlled  and  of  known  pedigree. 
The  result  was  that  in  every  case  castration  was  incomplete  and  ovarian  regeneration 
occurred,  leading  to  the  production  of  young  showing  no  influence  of  the  introduced 
graft. 


181 


ON  GERMINAL  TRANSPLANTATION  IN- 
VERTEBRATES 


W.  E.  CASTLE  AND  JOHN  C.  PHILLIPS 


WASHINGTON,  D.  C. 

PUBLISHED  BY  THE  CARNEGIE  INSTITUTION  OF  WASHINGTON 

1911 


ON  GERMINAL  TRANSPLANTATION  IN 
VERTEBRATES 


BY 


W.  E.  CASTLE  AND  JOHN  C.  PHILLIPS 


WASHINGTON,  D.  C. 

PUBLISHED  BY  THE  CARNEGIE  INSTITUTION  OF  WASHINGTON 

1911 


CARNEGIE  INSTITUTION  OF  WASHINGTON 
PUBLICATION  No.  144 


PAPER  No.  17  OF  THE  STATION  FOR  EXPERIMENTAL  EVOLUTION  AT 

COLD  SPRING  HARBOR,  NEW  YORK 

CONTRIBUTIONS  FROM  THE  LABORATORY  OF  GENETICS,  BUSSEY  INSTITUTION, 
HARVARD  UNIVERSITY,  No.  8. 


Copies  of  this  Book 
were  f »r$t  issued 

MAR  14 1911 


THE  COBNMAN  PRINTING   CO. 
CARLISLE,   PA. 


ON  GERMINAL  TRANSPLANTATION  IN  VERTEBRATES. 


1.  INTRODUCTION. 

The  scientific  results  described  in  this  paper  were  obtained  from  exper- 
iments begun  in  the  Zoological  Laboratory  of  Harvard  University  and 
completed  in  the  Laboratory  of  Genetics  of  the  Bussey  Institution.  These 
experiments  were  made  possible  by  a  grant  from  the  Carnegie  Institution 
of  Washington  to  the  senior  author,  for  which  grateful  acknowledgment 
is  hereby  made.  The  authors  desire  also  to  thank  Dr.  Alexis  Carrel,  of  the 
Rockefeller  Institute,  for  valuable  suggestions  as  to  operative  technique. 


The  curiosity  of  zoologists  has  long  been  aroused  to  know  whether  the 
reproductive  gland  of  a  vertebrate  can  be  successfully  transplanted  from 
the  body  of  one  individual  to  another;  and,  if  so,  whether  the  gland  will 
thereafter  function  in  its  new  environment;  and,  if  it  does,  whether  the 
nature  of  its  products  will  remain  unaltered.  The  fact  has  repeatedly  been 
pointed  out  that  experiments  of  this  sort,  if  successful,  should  afford  a 
crucial  test  of  the  Lamarckian  and  the  Weismannian  views,  respectively,  of 
the  relation  of  the  germinal  substance  to  its  environment  and  in  particular 
to  the  body. 

Our  own  attention  was  particularly  directed  to  these  questions  by  the  re- 
markable results  recently  described  by  Guthrie  and  Magnus,  which  seemed 
to  show  that  transplanted  ovaries,  in  a  foreign  body,  liberate  products  dis- 
tinctly influenced  in  nature  by  that  body.  To  test  the  correctness  of  such 
a  conclusion  the  experiments  described  in  this  paper  were  undertaken. 
Since  it  is  known  that  the  environment  directly  influences  the  nature  of 
the  body,  if  it  can  be  shown  further  that  the  body  directly  influences  the 
character  of  the  inheritance  through  the  sexual  products,  the  Lamarckian 
principle  is  established  and  that  of  Weismann  is  disproved.  It  is  therefore 
of  fundamental  importance  either  to  confirm  or  to  disprove  the  results  of 
the  authors  mentioned. 

We  are  unable  to  confirm,  we  present  evidence  which  tends  to  disprove, 
the  conclusions  reached  by  Guthrie  and  Magnus.  We  do  not  question  the 
results  reported  by  them,  but  only  the  interpretations  given  by  them  to  that 
work. 

Every  biologist  is  familiar  with  the  able  series  of  essays  in  which  Weis- 
mann showed  the  physiological  distinctness  of  body  and  germ-plasm.  Many 
will  recall  also  the  noteworthy  experiments  of  Heape  (1890-1897),  by  which 
he  showed  that  influences  exerted  during  gestation  do  not  modify  the  inher- 

1 


264GI4 


TRANSPLANTATION   INVERTEBRATES. 

itance.  Heape's  evidence  was  this:  The  fertilized  egg-  of  a  rabbit  of  one 
variety  (for  example  a  long-haired  albino)  was  removed  from  the  oviduct 
of  the  mother  before  it  had  become  attached  to  the  uterine  wall.  It  was 
then  transferred  immediately  to  the  oviduct  of  a  rabbit  of  a  different  vari- 
ety (for  example  a  Belgian  hare,  which  is  neither  white  nor  long-haired). 
In  several  cases  the  transferred  egg  became  attached  in  its  new  position 
and  passed  through  all  the  stages  of  gestation.  Young  rabbits  produced 
in  this  way  were  both  long-haired  and  albinos  like  the  mother  of  the  eggs, 
not  like  the  rabbit  which  bore  the  young.  The  foster-mother,  indeed,  seems 
not  to  have  influenced  the  inheritance  any  more  than  the  corn  supplied  to 
cattle  determines  their  breed  characters . 

Granting  all  this,  a  further  question  remains  to  be  dealt  with.  The 
transferred  egg  was  already  full-grown  and  fertilized.  If  the  transfer  had 
been  made  at  an  earlier  stage  while  the  egg  was  still  growing,  would  the 
results  have  been  the  same  ?  Might  not  the  growing  egg  have  lacked  that 
selective  power  in  assimilation  which  belongs  to  the  full-grown  and  fertil- 
ized egg  ?  May  not  the  former  be  subject  to  modification  by  the  environ- 
ment, even  though  the  latter  is  not? 

This  is  the  question  involved  in  a  study  of  germinal  transplantation. 
Guthrie  believes  that  he  has  found  evidence  of  such  modification;  we  ques- 
tion the  validity  of  this  evidence,  on  what  grounds  will  presently  appear. 
On  the  other  hand,  we  present  one  clear  case  of  the  transplantation  of  an 
undeveloped  ovary,  which  later  liberated  eggs  in  the  body  of  a  foster-mother, 
but  in  the  young  so  produced  no  foster-mother  influence  is  detectable.  We 
therefore  question  still  the  existence  of  foster-mother  influence.  We 
maintain  with  Weismann  not  only  that  modifications  of  the  body  are  not 
handed  on  to  the  germ-plasm,  but  that  the  character  of  the  body  does  not 
in  the  least  influence  the  character  of  the  contained  germ-plasm,  provided 
only  the  body  affords  a  suitable  medium  within  which  the  germ-plasm  may 
exist. 

2.  REVIEW   OF  THE   LITERATURE  ON  OVARIAN    GRAFTING   IN   ANIMALS 

OTHER  THAN  WAN. 

Beginning  with  the  year  1895,  a  large  number  of  investigators  have  given 
attention  to  ovarian  grafting.  The  results  have  often  been  conflicting.  They 
represent  the  work  of  physiologists,  pathologists,  biologists,  experimental 
and  clinical  surgeons,  and  lastly  of  students  of  heredity.  It  is  impossible 
here  to  give  space  for  the  discussion  of  the  entire  subject.  All  that  is  pro- 
posed is  a  brief  review  of  its  more  important  aspects. 

As  now  understood,  the  term  autoplastic  grafting  means  the  transfer  of 
tissue  within  the  body  of  the  individual,  while  homoplastic  means  the  trans- 
fer of  tissue  between  individuals  of  the  same  species.  A  third  term,  hetero- 
plastic  grafting,  is  used  to  denote  a  transfer  between  two  individuals  of 
different  species  or  genera. 

It  is  proposed  to  review  very  briefly  the  work  done  in  each  of  these  fields . 


OVARIAN    GRAFTING   IN    ANIMALS   OTHER   THAN   MAN.  3 

Knauer  (1896)  was  the  first  to  report  on  a  series  of  experiments  with  ani- 
mals. He  was  led  to  undertake  this  work  through  Chrobak,  a  surgeon  who 
had  himself  tried  feeding"  ovarian  substance  to  women  in  whom  an  artificial 
menapause,  with  its  attendant  train  of  symptoms,  had  been  brought  about  by 
operation.  Chrobak' s  results  were  not  conclusive,  and  he  thought  surgical 
grafting  held  out  more  hope  of  relief  in  these  cases. 

In  his  several  papers  (1896-1900)  Knauer,  who  worked  on  rabbits,  showed 
by  a  series  of  twelve  autografts  that  the  transplanted  ovary  persisted  in  its 
new  location  even  up  to  three  years;  that  its  appearance  was  normal;  that 
genital  atrophy  was  prevented;  and  further,  that  it  was  possible  for  animals 
so  operated  upon  to  bear  young.  He  gives  details  of  his  very  careful  tech- 
nique. The  ovaries,  after  the  castration,  were  placed  either  in  the  meso- 
metrium,  on  the  horn  of  the  uterus,  or  between  the  fascia  and  muscles  of  the 
abdominal  wall. 

Grigoryeff  (1897)  confirmed  Knauer' s  work  in  all  its  aspects  and  reported 
normal  young  born  from  his  rabbits  after  castration  and  autoplastic  removal 
of  both  ovaries. 

Ribbert  (1897-1898)  made  careful  his tological  examinations  of  autoplastic 
ovaries,  studying  the  initial  process  of  destruction  followed  by  reconstruc- 
tion. As  late  as  150  days  after  the  operation  he  found  no  atrophy. 

Fish,  Rubinstein,  Halban,  Herlitzka,  Basso,  Carmichael,  Katsch,  Still- 
ing, Limoii,  and  others  also  proved  that  autoplastic  grafting  is  possible. 
From  their  work  one  comes  to  the  conclusion  that  autografts  of  whole  ova- 
ries on  animals  should  nearly  always  be  successful,  provided  the  technique 
is  careful  and  the  ovary  not  too  large  or  too  old.  Success  does  not  appear 
to  depend  upon  the  new  position  of  the  ovary.  It  will  grow  anywhere 
where  nourishment  is  assured,  and  will  even  establish  itself  at  times  when 
merely  dropped  into  the  peritoneal  cavity.  In  connection  with  this,  one 
must  remember  the  experiment  of  Lode,  who  injected  the  ova  of  Ascaris 
into  the  abdominal  cavity  of  animals  and  afterwards  recovered  these  from 
the  fallopian  tubes  and  uterus. 

Among  all  these  workers  Arendt  raises  the  only  dissenting  voice.  He 
concludes  that  neither  autoplastic  nor  homoplastic  ovarian  grafting  is  pos- 
sible. He  criticizes  Knauer's  work  and  the  clinical  work  of  Glass,  Morris, 
Montprofit,  and  others,  but  his  conclusions  are  clearly  too  sweeping. 

We  have  ourselves  obtained  several  normal  young  from  a  rabbit  whose 
own  ovaries  were  grafted  onto  the  uterine  horns.  Both  the  ovaries  were 
found  large  and  healthy  in  their  new  position  at  the  end  of  nine  months. 

In  studying  the  results  of  homoplastic  grafting  we  obtain,  however,  a  very 
different  picture  and  are  forced  to  conclude  that  the  success  in  this  group 
depends  not  only  on  good  technique,  but  also  perhaps  on  the  relationship  of 
the  two  stocks,  and  certainly  on  the  intimate  chemical  tolerance  of  the 


4  ON  GERMINAL  TRANSPLANTATION  IN  VERTEBRATES. 

opposed  tissues.  Thus  the  results  are  greatly  at  variance.  No  doubt  the 
stock  used  by  some  of  the  workers  in  this  field  has  been  more  or  less  closely 
related.  The  ratio  of  success  in  such  cases  to  the  degree  of  relationship 
of  the  opposing  tissues  has  not  been  worked  out,  so  far  as  we  are  aware. 

It  is  necessary  to  criticize  workers  in  this  group  on  the  ground  that  many 
cases  are  considered  successful  if  the  ovary  is  found  more  or  less  normal 
after  short  intervals — days  or  weeks.  This  is  no  adequate  test,  as  in  many 
of  these  cases  degeneration  is  ultimately  complete. 

Knauer's  results  with  his  thirteen  operations  of  homoplastic  grafting  were 
negative  except  in  two  cases,  in  which  the  findings  were  by  no  means 
conclusive.  In  spite  of  this  Knauer  thought  tnat  homoplastic  grafts  were 
possible,  though  difficult. 

Fish  (1899)  experimented  upon  twenty  rabbits  with,  he  says,  successful 
results.  He  had  hoped  to  establish  the  fact  that  conception  is  possible 
subsequent  to  homoplastic  ovarian  transplantation,  but  in  this  he  was  dis- 
appointed. His  experiment  is  not  given  in  detail. 

Foa  (1900-1901)  was  led  to  undertake  experiments  in  homoplastic  graft- 
ing, at  the  suggestion '.  of  Celisea,  as  a  means  of  settling  the  controversy 
between  the  Neo-Lamarckians  and  the  Neo-Darwinians.  He  does  not  give 
details  of  each  experiment,  and  their  number  appears  to  have  been  small. 
His  grafts  were  made  onto  the  original  ovarian  sites.  With  this  method 
one  might  question  whether  regenerated  tissue  could  be  distinguished  from 
grafted  tissue.  His  conclusions  were  that  homoplastic  grafting  was  practical, 
especially  when  ovaries  of  new-born  animals  were  used  as  material  to  be 
grafted.  He  thought  that  such  material,  planted  into  older  animals,  grew 
much  faster  than  normally  and  soon  arrived  at  the  growth  stage  of  the 
host,  and  he  cites  an  experiment  in  support  of  this  view.  It  is  possible, 
however,  that  regeneration  of  older  tissue  may  have  occurred  in  such  cases 
rather  than  accelerated  development  of  introduced  tissue.  He  says  also 
that  ovaries  of  a  new-born  animal  immediately  degenerate  when  placed  in 
an  older  animal  whose  own  ovaries  have  ceased  to  function.  His  findings 
inclined  him  to  the  belief  that  there  can  not  be  such  independence  of  ger- 
minative  material  as  the  doctrine  of  Weismann  would  have  us  believe. 
Experiments  in  which  he  hoped  to  show  the  influence  of  the  foster-mother 
upon  foreign  germinative  material  have  not  been  heard  from. 

Guthrie  (1908)  did  homoplastic  grafting  of  ovaries  in  chickens  and  ob- 
tained young  from  his  grafted  animals.  He  concludes  that  the  homoplastic 
ovaries  function  normally  and  produce  young.  He  thinks  that  the  color 
characteristics  of  the  foetuses  and  of  the  chicks  may  be  influenced  by  the 
foster-mother.  The  detailed  observations  made  may  be  summarized  as 
follows : 

Two  pure-bred  black  single- comb  Leghorn  and  two  white  single-comb 
Leghorn  pullets  were  operated  upon,  and  a  third  pullet  of  each  sort  was 


OVARIAN   GRAFTING   IN   ANIMALS   OTHER   THAN   MAN.  5 

kept  as  control.  In  the  operations  the  ovary  of  a  black  pullet  was  exchanged 
with  that  of  a  white  one.  Six  months  after  the  operation  the  birds,  which 
had  now  begun  to  lay,  were  mated,  with  the  following-  results  in  chicks  or 
foetuses: 

1 .  The  control  black  hen  mated  with  a  black  cock  produced  thirteen  black 
chicks  with  light  breasts  and  throats. 

2 .  Black  hen  B  2 ,  which  had  received  an  ovary  from  a  white  pullet  and 
was  mated  with  a  white  cock,  produced  nine  white  chicks  and  eleven  white 
ones  having  black  spots  on  heads,  wings,  or  backs. 

3 .  Black  hen  B  3 ,  which  had  received  an  ovary  from  a  white  pullet  and 
was  mated  with  a  black  cock,  produced  four  ordinary  black  chicks  (with  light 
under  surfaces)  and  two  chicks  described  as  being  '  'black  with  white  legs. ' ' 

4.  The  control  white  hen  mated  with  a  white  cock  produced  eighteen 
white  chicks. 

5 .  White  hen  W  2 ,  which  had  received  an  ovary  from  a  black  pullet  and 
was  mated  with  a  white  cock,  produced  three  white  chicks,  one  chick  white 
with  black  spots,  and  one  ordinary  black. 

6.  White  hen  W3,  which  had  received  an  ovary  from  a  black  pullet  and 
was  mated  with  a  black  cock,  produced  twelve  white  chicks  spotted  with 
white  on  head,  wings,  or  back. 

The  conclusions  to  be  drawn  from  these  observations  will  be  discussed 
elsewhere  in  this  paper. 

Magnus  (1907)  transferred  the  ovaries  from  an  albino  to  a  black  rabbit 
with  apparent  success.  The  black  rabbit  was  mated  with  an  albino  male 
five  months  after  the  operation  and  a  month  later  bore  two  young,  one 
black  and  the  other  an  albino.  Two  months  later  she  died  pregnant,  and 
in  the  uterus  were  found  two  dark-colored  embryos  and  five  light-red  ones 
supposed  to  be  albinos.  No  ovary  was  found  on  one  side  of  the  body,  but 
on  the  other  side  was  a  well-developed  and  functional  ovary  bearing  corpora 
lutea.  Magnus  supposes  that  all  the  embryos  produced  were  derived  from 
eggs  liberated  by  the  transplanted  ovary,  but  in  view  of  our  own  experience 
we  are  inclined  to  question  this  interpretation. 

Ten  other  rabbits  similarly  grafted  by  Magnus  produced  no  young,  though 
three  of  them  gave  indications  by  their  sexual  activity  that  they  contained 
living  ovarian  tissue. 

Among  other  authors  who  have  reported  successful  results  with  homo- 
plastic  grafting  in  animals  may  be  mentioned:  Schaus,  Basso,  Mauclaire, 
McCone,  and  Lukaschewitsch. 

McCone  gives  the  case  of  the  birth  of  five  well-formed  offspring  in  a  rab- 
bit from  the  grafted  ovary  of  another  rabbit,  but  the  evidence  that  the  func- 
tioning ovary  was  an  introduced  ovary  is  far  from  complete.  Pregnancy 
took  place  four  months  after  complete  castration  and  transplantation  from 
another  member  of  the  same  species.  The  other  authors  report  no  young. 


6          ON  GERMINAL  TRANSPLANTATION  IN  VERTEBRATES. 

At  variance  with  these  results  are  the  work  of  the  following- :  Marchese, 
Herlitzka,  Marshall  and  Jolly,  Burckhardt,  and  Preobrazhenski,  in  whose 
work  degeneration  of  the  implanted  foreign  ovary  was  complete  or  nearly 
so  after  short  intervals. 

The  work  on  heteroplastic  ovarian  grafting-  is  small  in  amount,  and  the 
evidence,  taken  as  a  whole,  makes  it  safe  to  say  that  persistence  of  normal 
tissue  after  a  few  days  or  weeks  is  very  rare. 

Bucura  (1907)  reports  the  most  favorable  results.  He  transplanted  ova- 
ries of  guinea-pigs  into  castrated  female  rabbits.  In  the  first  of  his  three 
cases  he  found  after  eight  weeks  the  uterus  atrophied,  but  some  evidence 
of  ovarian  tissue  without  follicles.  Another,  rabbit  (similarly  treated) 
was  killed  after  fifty-one  days.  In  this  animal  there  was  no  genital  atro- 
phy, and  one  of  the  guinea-pig  ovaries  showed  some  normal  follicles  and 
a  well-developed  corpus  luteum.  The  other  was  completely  atrophied. 
In  the  third  case,  after  seventy-seven  days,  one  of  the  grafted  guinea-pig 
ovaries  was  completely  resorbed,  the  other  nearly  so;  while  atrophy  was 
advanced  in  the  rabbit  uterus.  The  author  thinks  that  heteroplastic  trans- 
plantation is  possible. 

Basso  (1905)  reports  negative  results  in  grafting  ovaries  between  guinea- 
pigs  and  rabbits. 

McCone  (1899)  cites  a  case  of  persistence  of  the  ovaries  of  a  bitch  in  a 
female  rabbit  for  three  and  a  half  months  with  prevention  of  genital  atrophy 
in  the  rabbit.  He  gives  an  illustration  of  this  ovarian  tissue. 

Lukaschewitsch  (1901)  believes  that  it  is  possible  to  transplant  ovaries 
from  carnivorous  to  herbivorous  animals  and  vice  versa,  and  that  genital 
atrophy  may  be  prevented.  He  obtained  no  young  from  animals  so  oper- 
ated upon,  and  does  not  describe  his  operations  in  detail. 

3.  REVIEW  OF  THE  LITERATURE  ON  OVARIAN  GRAFTING  IN  MAN. 

It  is  not  surprising  when  we  turn  to  the  clinical  experiments  to  find  that 
autograf ts  in  women  are  by  no  means  always  successful .  The  material  to 
be  grafted  has  been  adult,  and  the  organ  often  affected  by  tumor  growth  or 
cystic  and  atrophic  changes.  Small  wedges  of  the  organ  have  been  used. 

Many  authors  have  advocated  conservative  surgery  in  order  to  avoid  the 
bad  effects  of  precipitate  menapause,  but  too  often  cases  of  this  sort  have 
been  reported  as  successful  when  the  after  history  was  incomplete.  It  is 
safe  to  say  that  autografting  of  ovarian  tissue  in  women  has  not  given 
nearly  such  uniform  results  as  in  animals  under  experimental  conditions. 

Menstruation  has  been  said  to  persist  in  as  many  as  20  per  cent  of  all  cases 
of  ovariotomy.  Furthermore,  there  are  numerous  cases  reported  of  preg- 
nancy after  complete  ovariotomy.  Doran  (1902)  cites  three  such  cases.  In 
one  of  these,  observed  by  himself,  a  definite  focus  of  extra-ovarian  tissue 
was  found  at  a  second  operation  in  the  ovarian  ligament. 


OVARIAN   GRAFTING    IN    MAN.  7 

Dauber  (1905)  shows  how  difficult  it  is,  especially  in  disease,  to  assert 
with  confidence  ttiat  all  ovarian  tissue  has  been  removed. 

Dudley  (1900)  cites  several  cases  of  pregnancy  after  ovariotomy. 

Croom  (1905)  reports  a  case  of  homoplastic  ovarian  graft,  with  four  years 
later  the  birth  of  a  living-  child.  Obviously  it  is  impossible  to  verify  such 
cases  as  this,  and  they  must  always  remain  open  to  doubt  unless  the  child  in 
question  shows  some  strongly  inherited  and  dominant  characteristic  which 
was  possessed  by  the  individual  who  supplied  the  graft,  but  not  by  the 
foster-mother  or  by  the  father.  Such  conditions  are  not  likely  often  to  be 
realized  in  clinical  experience,  hence  our  principal  reliance  for  determin- 
ation of  the  theoretical  questions  involved  must  be  animal  experimentation. 

Morris  (1906),  who  had  done  much  successful  clinical  work  on  autograft- 
ing,  besides  some  early  experimental  work,  reported  the  birth  of  a  living 
child  in  a  woman  into  whom,  after  careful  castration  with  the  Tuffier  angio- 
tribe,  he  had  grafted  wedges  of  ovary  from  another  woman.  The  castrated 
ovaries  of  the  woman  who  was  grafted  were  cirrhotic,  and  no  formed 
Graafian  vesicles  were  found.  It  was  assumed  that  the  introduced  ovarian 
tissue  was  responsible  for  the  result  reported;  but  Lucas-Championniere, 
criticizing  this  case,  has  expressed  the  view  that  it  can  be  given  another 
interpretation.  He  cites  as  an  example  a  patient  of  his  own,  in  whom,  after 
the  most  careful  castration  with  the  angiotribe  for  a  case  of  dysmenorrhea, 
the  symptoms  still  persisted.  A  second  operation  on  this  patient,  over  a 
year  later,  revealed  an  important  ovarian  fragment  at  the  uterine  horn. 

Glass  (1899)  gives  a  convincing  case  of  homoplastic  operation  in  a  woman 
who  two  years  before  had  had  ovariotomy  performed.  She  was  suffering 
from  all  the  symptoms  of  an  artificial  menapause,  but  a  graft  from  another 
woman  relieved  her.  The  relief  appears  to  have  been  permanent.  No 
children  are  reported. 

Mauclaire  (1900)  collected  thirteen  cases  of  homoplastic  operation  in 
women.  In  six  of  these  cases  menstruation  returned,  and  in  two  cases  it 
was  resumed  temporarily.  The  persistence  and  functioning  of  the  intro- 
duced tissue  is,  however,  in  no  case  established  beyond  question.  On  the 
whole,  Mauclaire  regards  ovarian  transplantation  as  of  doubtful  clinical 
value. 

Sauve*  (1910)  sums  up  in  a  very  clear  and  direct  way  all  the  surgical  evi~ 
dence  at  hand.  His  statistics  show  that  return  of  menstruation  is  no  more 
common  after  ovarian  grafting  than  after  ovarian  castration.  There  are, 
he  thinks,  only  two  cases  of  successful  homoplastic  grafting  in  women. 
The  first  case  is  that  reported  by  Morris,  in  which  a  woman  with  infantile 
ovaries  became  normal  and  had  regular  menstruation  after  the  transfer  of 
ovarian  tissue  from  another  woman;  and  the  second  case  is  that  of  Pankow, 
which  is  supported  by  definite  histological  evidence  after  a  period  of  three 
years. 


8  ON   GERMINAL   TRANSPLANTATION   IN   VERTEBRATES. 

4.  NEW  OBSERVATIONS  ON  OVARIAN  GRAFTING. 

In  this  paper  we  shall  report  upon  seventy-four  cases  of  homoplastic 
ovarian  grafting-  in  guinea-pigs  and  seventeen  similar  cases  in  rabbits. 
The  purpose  of  the  experiments  represented  by  these  cases  has  been  stated 
in  the  introduction. 

The  operative  technique  in  the  guinea-pig  was  as  follows:  The  hair  of 
the  female  to  be  grafted  was  removed  from  each  side  at  the  costal  border. 
She  was  then  anesthetized  and  was  castrated  through  an  incision  on  each 
side,  about  an  inch  long,  at  the  costal  border  and  usually  a  little  ventral  to 
the  ovarian  site.  The  ovary  was  drawn  into  the  field  with  blunt  forceps 
and  lifted  with  a  small,  double  eye-hook,  after  having  been  carefully  shelled 
out  from  the  tube  and  mesentery.  The  organ  was  then  cut  away,  care 
being  taken  not  to  damage  the  tube.  The  animal  from  which  grafts  were 
to  be  taken  was  then  quickly  killed  and  its  ovaries  removed,  but  with  a  small 
bit  of  mesentery  attached.  The  ovaries  themselves  did  not  come  into  con- 
tact with  any  instrument.  They  were  attached  by  means  of  very  fine  silk 
(OO  untwisted  into  thirds)  and  a  header's  needle,  to  various  sites  in  the 
peritoneal  cavity.  Some  even  were  merely  dropped  into  the  abdominal 
cavity.  The  muscles  and  skin  were  closed  separately.  At  first  two  opera- 
tions were  made  for  each  animal,  but  this  was  soon  found  to  be  unneces- 
sary. The  mortality  was  very  slight.  Out  of  the  seventy-four  cases  six 
died  as  the  immediate  result  of  the  operation;  four  of  these  were  cases  in 
which  a  ventral  incision  was  tried. 

To  sum  up  the  result  of  the  entire  series,  only  one*  grafted  animal  had 
young  from  her  grafted  tissue;  grafted  ovaries  functioned  in  six  other  cases, 
but  did  not  produce  young.  Ten  animals  regenerated  their  own  ovaries, 
and  three  of  these  had  young.  Forty-two  showed  post-mortem  complete 
atrophy  of  the  genital  tract  and  absence  of  ovarian  tissue.  The  remainder 
comprises  fifteen  cases  in  which  results  were  not  fully  determined. 

It  is  thought  worth  while  to  give  an  account  of  all  the  groups,  because, 
though  only  one*  case,  Group  I,  bears  on  the  problem  before  us,  the  series 
may  have  some  physiological  significance  on  account  of  its  very  consider- 
able size,  and  may  throw  a  side-light  upon  what  criteria  are  necessary  in 
such  work. 

GROUP  I. 

This  group  includes  homoplastic  transplantation  of  an  ovary  resulting 
in  the  birth  of  young  derived  from  grafted  tissue.  On  January  6,  1909, 
the  left  ovary  was  removed  from  an  albino  guinea-pig,  No.  27  (fig.  2,  pi.  l), 
then  about  5  months  old,  and  the  ovary  of  a  pure  black  gtiinea-pig  (compare 
fig.  1,  pi.  1),  about  a  month,  old  was  fastened  near  the  tip  of  the  uterine 
horn,  distant  a  centimeter  or  more  from,  the  site  of  the  ovary  removed.  One 
week  later,  January  13,  a  second  operation  was  performed,  in  which  the 
right  ovary  of  the  albino  was  removed,  and  as  a  graft  was  introduced  the 

A  second  case,  from  a  new  series  of  experiments,  has  just  been  observed  (January, 
1911) ;  see  Postscript,  p.  10. 


NEW   OBSERVATIONS   ON   OVARIAN   GRAFTING.  9 

ovary  of  a  second  young  black  guinea-pig-,  of  like  age  with  the  first  but  of 
different  ancestry.  *  After  the  albino  had  fully  recovered  from  the  second 
operation,  she  was  placed  with  an  albino  male,  No.  654  (fig.  3,  pi.  l)  with 
which  she  remained  until  her  death  about  a  year  later. 

On  the  23d  of  July,  198  days  after  the  first  operation,  she  gave  birth  to 
two  female  young.  One  was  black  but  bore  a  few  red  hairs.  A  photograph 
of  this  animal  (No.  1970)  at  the  age  of  three  or  four  months  is  shown  in 
fig.  6,  pi.  2.  The  other  young  one  (No.  1969)  was  likewise  black,  but  had 
some  red  upon  it,  and  its  right  forefoot  was  white.  (See  fig.  5,  pi.  2.) 

On  October  15  the  grafted  albino  bore  a  third  black  young  one,  a  male 
which,  like  those  previously  born,  had  a  few  red  hairs  interspersed  with  the 
black.  A  photograph  of  this  animal  is  shown  in  fig.  4,  pi.  2. 

On  January  11,  1910,  the  grafted  albino  was  observed  to  be  pregnant  for 
the  third  time,  and  this  time  she  was  very  large.  Unfortunately,  on  Feb- 
ruary 2,  she  died  of  pneumonia  with  three  full-grown  male  young  in  utero. 
The  skins  of  these  animals  were  saved  and  a  photograph  of  them  is  shown 
in  figs.  7-9,  pi.  2.  Like  the  other  three  young  they  were  black,  but  with 
a  few  red  hairs  among  the  black  ones.  They  bore  no  white  hairs. 

An  autopsy  made  one  hour  after  the  death  of  the  mother  showed  on  the 
left  side  a  distinct  ovarian  mass  about  a  centimeter  from  the  coiled  part  of 
the  oviduct;  that  is,  approximately  in  the  position  where  the  graft  from  the 
pure  black  guinea-pig  was  fastened  at  the  first  operation.  On  the  right 
side  the  mesentery  of  the  oviduct  was  adherent  to  the  body-wall  where 
an  incision  had  been  made  at  the  second  operation,  and  a  small  amount  of 
tissue,  regarded  as  possibly  ovarian,  was  there  observed.  Both  this  and 
the  ovarian  tissue  from  the  left  side  were  preserved  in  Gilson's  fluid  for 
sectioning  and  microscopic  examination.  The  tissue  from  the  left  side  was 
found  to  contain  numerous  large  egg-follicles,  some  already  well  advanced 
containing  a  lymph  space;  in  addition  a  number  of  corpora  lutea  were 
observed.  On  the  right  side  was  found  a  small  amount  of  undoubted  ova- 
rian tissue,  with  one  well -advanced  egg-follicle,  but  the  whole  apparently 
was  strongly  encapsulated,  so  that  no  eggs  could  be  discharged  even  if  they 
came  to  maturity. 

It  is  interesting  to  note  that  both  grafts  persisted,  though  taken  from 
different  animals  and  transferred  at  different  times.  This  result  suggests 
a  possible  susceptibility  on  the  part  of  the  animal  grafted. 

Female  1970  (fig.  6,  pi.  2)  daughter  of  the  grafted  albino,  was  mated 
with  the  albino  male,  her  father  (fig.  3,  pi.  l),  and  bore  three  young,  two 
of  which  were  albinos  and  one  black  with  some  red  hairs.  If  female  1970 
had  been  the  daughter  of  a  pure-black  mother,  instead  of  a  grafted  albino, 
we  should  have  expected  her  to  produce  an  equality  of  black  and  of  albino 
young.  The  observed  result  was  the  nearest  possible  numerical  agree- 
ment with  this  expectation. 

A  control  mating  of  the  albino  male,  654,  was  made  with  a  female  of 
pure  black  stock.  As  a  result  there  were  produced  two  litters  of  young, 


10         ON  GERMINAL  TRANSPLANTATION  IN  VERTEBRATES. 

including"  five  individuals,  all  black,  but  with  red  hairs  interspersed.  This 
result  shows  that  the  red  hairs  found  on  the  six  young  of  the  grafted  albino 
were  due,  not  to  foster-mother  influence  of  the  grafted  albino,  but  to  influ- 
ence of  the  male  parent.  The  young  of  the  grafted  mother  were  exactly 
such  in  color  as  the  black  guinea-pig  which  furnished  the  graft  herself 
might  have  been  expected  to  bear  had  she  been  mated  with  male  654  instead 
of  being  sacrificed  to  furnish  the  graft.  The  white  foot  borne  by  one  of  the 
young  forms  no  exception  to  this  statement.  Spotting  characterized  the  race 
of  guinea-pigs  from  which  the  father  came.  He  was  himself  born  in  a  litter 
which  contained  spotted  young,  whereas  neither  the  pure-bred  black  race 
that  furnished  the  graft  nor  the  albino  race  t£at  received  it  was i  character- 
ized by  spotting. 

Inasmuch  as  the  offspring  of  albino  parents  are  invariably  albinos,  it  is 
certain  that  the  six  pigmented  offspring  of  the  grafted  female  were  all 
derived  from  ova  furnished  by  the  introduced  ovarian  tissue  taken  from  a 
black  guinea-pig.  This  tissue  was  introduced  while  the  contained  ova  were 
still  quite  immature,  and  it  persisted  in  its  new  environment  for  nearly  a 
year  before  the  eggs  were  liberated  which  produced  the  last  litter  of  three 
young.  These  young,  like  the  earlier  litters,  gave  no  indication  of  foster- 
mother  influence  in  their  coloration. 

The  conclusion  is  forced  upon  us  that  the  egg-cell  during  its  growth  does 
not  change  in  germinal  constitution.  Its  growth  is  like  the  growth  of  a 
parasite  or  of  a  wholly  independent  organism  :  what  it  takes  up  serves  as 
food;  this  is  not  incorporated  merely  in  the  growing  organism;  it  is  made 
over  into  the  same  kind  of  living  substance  as  composes  the  assimilating 

organism. 

POSTSCRIPT. 

While  this  paper  was  in  press  a  second  case,  from  a  new  series  of  experi- 
ments, belonging  in  Group  I  came  to  light. 

An  albino  female,  No.  2475,  born  on  the  22d  of  March,  1910,  at  75  days  of 
age  was  operated  upon,  being  doubly  castrated  and  receiving  the  ovaries 
from  a  half-sister,  No.  2507,  a  brown-eyed  cream  animal,  17  days  younger 
than  herself.  She  was  then  mated  with  an  albino  male,  her  half-brother, 
No.  2402.  On  October  20,  136  days  after  the  operation,  she  gave  birth  to 
an  albino  young  one.  We  considered  this  an  indication  that  the  castration 
had  been  imperfect,  but  allowed  the  animal  to  breed  again.  Much  to  our 
surprise,  73  days  later,  on  January  1,  1911,  she  gave  birth  to  two  young, 
one  of  which  was  a  brown-eyed  cream  like  the  animal  which  furnished  the 
graft.  The  other  young  was  an  albino. 

The  albino  young  borne  by  this  grafted  animal  can  not  properly  be 
regarded  as  evidence  of  somatic  influence  on  the  introduced  graft.  For 
albinism  occurred  as  a  recessive  character  in  the  particular  brown-eyed 
cream  stock  used,  as  is  evident  from  the  fact  already  stated  that  the  colored 
animal  which  furnished  the  graft  and  the  albino  which  received  it  were 
half-sisters.  The  character  of  the  young  obtained  and  their  numerical  pro- 
portions are  exactly  such  as  the  colored  animal  would  herself  have  been 
expected  to  give,  had  she  not  been  sacrificed  to  furnish  the  grafts,  but  had 
been  mated  with  the  albino  male. 


CASTLE 


PLATE  1 


1 .  A  Young  Black  Guinea- Pig,  about  three  weeks  old.      Ovaries  taken  from  two 

animals  like  this  were  transplanted  into  the  albino  shown  in  Fig.  2. 

2.  An  Albino  Female  Guinea-Pig,  No.  27.  Its  ovaries  were  removed  and  in  their  place 

were  introduced  ovaries  from  two  young  black  guinea-pigs.     Compare  Fig.  1 . 

3.  An  Albino  Male  Guinea-Pig,  No.  654,  with  which  was  mated  the  albino  shown 

in  Fig.  2. 


CASTLE 


PLATE  2 


5    I 


4,  5,  and  6.  A  Group  of  Three  Young,  produced  by  the  pair  of  albinos  shown  in 
Figs.  2  and  3.  4,  is  female  1969,  5,  is  female  1970,  6,  is  the  male  born  on 
October  15.  All  were  about  half  grown  when  photographed. 

7,  8,  and  9.  Skins  of  three  young  found  in  utero  at  the  autopsy  of  female  No.  27, 
Fig.  2.  The  sire  of  these  young  also  was  male  No.  654,  Fig.  3. 


NEW   OBSERVATIONS   ON   OVARIAN   GRAFTING.  11 

GROUP  II. 

In  this  group  are  included  grafted  females  which  bore  no  young1  but  in 
which,  post  mortem,  there  was  found  ovarian  tissue  remaining:  from  the 
grafts.  Of  these  there  are  six  cases.  It  is  not  possible  in  each  case  to  say 
why  no  young  resulted.  In  five  cases  the  egg-follicles  were  well  developed, 
but  there  is  some  evidence  of  the  encapsulation  of  the  graft.  The  age  of 
these  animals  varies  from  three  months  to  a  year.  Their  own  ovaries  had 
been,  of  course,  always  first  removed  before  the  transplantation  was  made. 

Guinea-pig-  No.  40,  age  four  weeks,  was  grafted  from  an  animal  three 
weeks  old.  One  ovary  was  sutured  to  the  body- wall  near  the  incision  on 
the  right  side.  The  other  was  dropped  into  the  abdominal  cavity.  Nine 
months  later  the  animal  was  killed  and  found  to  have  a  healthy  uterus. 
At  the  right  body- wall  was  a  suspicious  nodule,  which  was  preserved  for 
reference.  Tissue  at  the  right  ovarian  site  was  also  saved.  Microscopic 
examination  showed  the  specimen  from  the  body-wall  to  contain  much 
ovarian  tissue  and  numerous  Graafian  follicles.  The  right  ovarian  site 
showed  no  ovarian  tissue. 

Guinea-pig-  No.  61,  age  one  year,  was  grafted  from  a  younger  animal, 
exact  age  not  stated.  The  grafts  were  placed,  one  loose  in  the  abdominal 
cavity,  and  one  stitched  to  the  muscle  wall  on  the  right  side  near  the  in- 
cision. Five  and  a  half  months  later  the  animal  was  killed.  Her  uterus 
was  found  large  and  healthy,  and  on  the  right  body-wall  was  a  vesiculated 
mass  20  mm.  long,  containing  what  appeared  to  be  the  transplanted  oviduct 
in  a  state  of  hydrosalpinx,  together  with  a  small,  pink,  hard  mass  at  one  end. 
Later  this  mass  was  found  to  be  ovarian.  One  young  egg-cell  in  its  fol- 
licle was  seen.  A  specimen  of  the  right  ovarian  site  showed  no  ovarian 
tissue. 

Guinea-pig  No.  21,  age  six  months,  was  grafted  from  an  animal  one 
month  old.  The  grafts  were  attached  one  on  each  side,  to  mesentery  close 
to  the  horn  of  the  uterus.  Four  and  a  third  months  later  the  animal  was 
examined,  and  both  grafted  ovaries  were  found,  easily  identified  by  their 
position.  The  uterus  was  in  the  stage  of  heat,  and  microscopic  examin- 
ation showed  both  ovaries  to  contain  Graafian  follicles.  One  egg  was  found 
undergoing  a  maturation  division.  There  was  no  ovarian  tissue  at  either 
original  ovarian  site. 

Guinea-pig  No.  53,  eight  months  old,  was  grafted  from  an  animal  one 
month  of  age;  the  operation  was  a  double  one,  that  on  the  right  side  being 
done  one  week  after  that  on  the  left  side.  The  ovaries  were  attached,  one 
on  each  side,  to  the  mesentery  at  the  uterine  horn.  Four  months  later  the 
animal  showed  a  large  uterus  in  the  stage  of  heat,  and  on  the  right  side 
was  found  the  grafted  ovary,  small  and  pale.  It  contained  many  large 
Graafian  follicles.  There  was  no  other  ovarian  tissue  found  anywhere. 

Guinea-pig  No.  47,  three  months  old,  was  grafted  from  an  animal  three 
weeks  old.  Both  the  ovaries  were  dropped  into  the  body-cavity  through  the 


12         ON  GERMINAL  TRANSPLANTATION  IN  VERTEBRATES. 

left  incision.  Ten  and  a  half  months  later  the  animal  was  killed.  The 
uterus  was  well  nourished.  There  was  no  tissue  at  the  sites  of  the  original 
ovaries,  but  attached  to  the  border  of  the  greater  omentum  was  a  typical 
ovarian  mass  which  showed  microscopically  plenty  of  ovarian  tissue  and 
at  least  one  large  ovarian  follicle.  This  case  is  interesting  as  showing  that 
presence  of  ovarian  tissue  in  immediate  contact  with  the  genital  ducts 
is  not  necessary  to  prevent  atrophy  of  those  ducts.  An  ovary  attached  to 
the  digestive  tract  (or  doubtless  anywhere  else  in  the  body)  serves  equally 
well  to  prevent  genital  atrophy.  Some  substance  liberated  by  the  ovary 
and  circulating  in  the  blood  is  doubtless  the  active  agent  in  maintaining 
the  full  development  of  the  uterus  and  the  recurrence  of  rut. 

In  guinea-pig  No.  73,  one  year  old,  the  grafts  were  placed,  one  attached 
to  the  right  body- wall,  the  other  merely  dropped  into  the  abdominal  cavity. 
Nine  and  a  half  months  later  the  animal  was  killed.  There  was  little  or 
no  genital  atrophy,  and  at  the  site  of  the  graft  on  the  body- wall  a  small 
mass  was  found  which  was  identified  by  microscopic  examination  as  the 
oviduct  of  the  graft,  with  a  small  amount  of  degenerating  ovarian  tissue, 
without  follicles.  There  was  no  sign  of  regenerated  tissue  at  the  ovarian 
sites . 

The  above  six  cases  show  that  normal  ovarian  tissue  persisted  in  its  new 
environment  for  periods  from  four  months  to  ten  and  a  half  months.  They 
demonstrate  that  the  position  of  a  homoplastic  graft  may  be  varied  to  any 
place  on  the  peritoneal  surface;  and  that  the  grafted  ovary  may  attach  and 
nourish  itself  without  the  aid  of  sutures. 

The  failure  of  these  foreign  ovaries  to  bring  about  pregnancy  inclines 
one  to  the  idea  that  the  ovum  when  mature  and  liberated  may  be  more 
subject  to  resorption  during  its  migration  to  the  uterus  than  the  more  prim- 
itive tissue  from  which  it  was  discharged.  It  is  also  well  to  remember  that 
Graafian  follicles  have  been  found  to  be  less  in  number  and  larger  in  size 
in  grafted  tissue  than  in  normal  tissue  (Carmichael,  Sauve).  Further, 
in  the  case  of  an  ovary  removed  from  its  normal  position,  the  chances  are 
necessarily  greatly  diminished  that  the  egg  when  liberated  will  find  its  way 
into  the  oviduct.  In  an  ovarian  operation  there  is  also  great  danger  that 
the  open  end  of  the  oviduct  will  become  permanently  closed  in  consequence 
of  injury.  On  the  whole  it  is  not  surprising  that  foreign  ovaries  often 
persist  without  bringing  about  pregnancy. 

GROUP  III. 

This  group  includes  ten  cases  in  which,  in  spite  of  a  supposed  perfect 
castration,  the  animal  regenerated  ovarian  tissue  at  the  original  site.  Three 
of  these  animals  bore  young.  In  all  ten  cases  regenerated  ovaries  were 
found  post  mortem  by  inspection  and  microscopic  examination.  The  color- 
character  of  the  young  indicated  that  they  had  probably  come  from  regen- 
erated tissue,  and  the  autopsy  in  all  cases  confirmed  this  view. 


NEW   OBSERVATIONS   ON   OVARIAN   GRAFTING.  13 

The  three  cases  ii}  which  young-  were  born  are  as  follows : 

Guinea-pig  No.  77,  blue,  age  five  months,  underwent  a  double  ovarian 
operation  in  which  grafts  were  taken  from  a  pale  cinnamon  agouti  guinea- 
pig,  age  one  week.  Both  grafts  were  placed  on  the  right  side  at  the  uterine 
horn.  Six  months  later  she  bore  by  a  white  male,  No.  654  (fig.  3,  pi.  l), 
a  blue  female  young  one.  She  was  killed  eight  months  after  the  operation 
and  ovarian  tissue  was  demonstrated  at  the  right  ovarian  site,  while  the 
graft  had  completely  disappeared. 

Guinea-pig  No  24,  an  albino,  age  four  weeks,  was  grafted  from  a  black 
animal  one  day  old.  One  graft  was  stitched  to  the  body-wall  on  each  side. 
Two  and  a  half  months  later  she  was  noted  pregnant,  and  at  three  months 
she  had,  by  male  1078  (a  brown-eyed  yellow),  two  young,  both  black-eyed 
yellow.  Her  post  mortem  two  days  later  showed  indications  of  ovarian 
tissue  at  both  ovarian  sites,  but  the  microscopic  examination  showed  that 
ovarian  tissue  was  confined  to  the  right  ovarian  site.  There  was  nothing 
left  of  either  graft. 

Guinea-pig  No.  1907,  black,  age  three  weeks,  whose  parents  were  one 
black ,  the  other  cinnamon  agouti  marked  with  cream,  was  grafted  with 
ovaries  from  a  cinnamon  agouti,  age  five  days.  One  graft  was  dropped 
into  the  abdominal  cavity,  and  one  was  attached  to  the  body-wall  on  the 
right  side  near  the  incision.  Five  months  later  she  bore,  when  mated  to  male 
No.  654,  fig.  3,  a  young  black  male  with  red  brindling.  The  post-mortem 
showed  at  the  right  body- wall  a  pinkish  mass  1.5  mm.  in  diameter,  which 
was  preserved.  Both  ovarian  sites  were  also  saved  for  microscopic  exam- 
ination. The  peritoneal  cavity  was  negative.  The  microscope  showed 
that  the  mass  on  the  body-wall  consisted  of  much  fibrous  and  connective 
tissue  penetrated  by  blood-vessels,  the  remains  of  the  degenerated  graft. 
The  right  ovarian  site  showed  normal  ovarian  tissue  with  Graafian  follicles 
present. 

The  other  seven  cases,  in  which  no  young  were  produced,  but  in  which 
the  presence  of  regenerated  ovarian  tissue  was  demonstrated  by  the  micro- 
scope, need  not  be  given  in  detail.  A  well-developed  condition  of  the  uterus 
was  observed  in  all. 

GROUP  IV. 

In  this  group  are  included  those  cases,  forty- three  in  all,  which  showed, 
by  complete  atrophy  of  the  genital  tract,  absence  of  all  ovarian  tissue.  Care- 
ful microscopic  inspection  was  made  in  all  cases,  but  nothing  resembling 
ovarian  tissue  was  in  any  case  observed.  Four  of  these  animals  died  from 
two  to  nine  months  after  the  operation;  the  remainder  were  killed  at  periods 
ranging  from  four  months  to  one  year  afterward.  The  average  age  of  the 
lot  at  the  time  of  the  operation  was  eight  weeks.  The  individual  age  of 
the  transplanted  ovaries  varied  from  one  day  to  two  months,  while  the 
average  age  was  three  weeks. 


14         ON  GERMINAL  TRANSPLANTATION  IN  VERTEBRATES. 

GROUP  V. 

In  this  gfroup  are  placed  fifteen  cases  in  which  the  grafted  animals  died 
or  were  lost  without  any  autopsy  being-  made  upon  them.  Only  six  died 
as  the  immediate  result  of  the  operation,  four  of  the  six  being  cases  in  which 
a  ventral  route  to  the  ovaries  was  attempted. 


The  results  obtained  by  iis  from  ovarian  grafting  in  rabbits  are  largely 
negative.  Seventeen  animals  have  been  operated  upon. 

One  rabbit,  in  which  an  autograft  was  made  onto  the  uterine  horn  on  each 
side,  gave  birth  four  months  later  to  two.young.  Nine  months  later  a 
second  operation  showed  both  these  autografts  functioning ;  they  were 
removed  and  ovaries  from  another  rabbit  were  placed  in  their  stead;  atrophy 
of  the  external  genitalia  soon  resulted  and  the  animal  was  a  few  months 
later  discarded.* 

Of  the  other  homoplastic  cases,  two  showed  regenerated  tissue  at  the 
original  ovarian  site,  one  of  these  having  had  young.  Of  the  remainder, 
six  died  or  were  lost,  while  three  showed  complete  atrophy  of  the  external 
genitalia  and  three  more  are  still  alive,  manifesting  normal  sexual  instincts 
but  having  borne  as  yet  no  young. 

On  the  whole  the  results  obtained  from  rabbits  are  very  similar  to  those 
obtained  from  guinea-pigs.  Autografting  is  evidently  not  difficult,  and 
may  be  followed  by  the  birth  of  young.  In  heteroplastic  grafting,  regener- 
ation of  ovarian  tissue  at  the  original  site  is  a  commoner  event  than  growth 
of  the  introduced  tissue,  the  latter  result  not  having  been  certainly  obtained 
in  our  experiments  with  rabbits,  though  the  former  has  been  obtained  in 
two  cases. 

5.  CRITICAL  EXAMINATION  OF  THE  OBSERVATIONS  OF  GUTHRIE   AND  MAGNUS  ON 
SUPPOSED  FOSTER-MOTHER  INFLUENCE. 

A  cursory  reading  of  Outline's  evidence  may  well  lead  one  to  accept 
without  question  his  conclusions:  (l)  that  in  his  fowls  the  transplanted 
ovaries  have  functioned,  and  (2)  that  the  foster-mother  has  influenced  the 
character  of  the  young;  but  critical  analysis  of  the  evidence  fails  to  sub- 
stantiate either  conclusion.  Since  the  ovaries  exchanged  were  transplanted 
to  the  original  ovarian  site,  it  would  have  been  impossible  by  autopsy  to 
ascertain  whether  the  ovary  present  was  transplanted  or  regenerated 
tissue.  But  regeneration  is  a  much  commoner  result  of  such  operations 
than  successful  transplantation,  as  our  results  with  guinea-pigs  show;  and 
in  the  absence  of  other  evidence  the  interpretation  of  the  functioning  ovary 
as  a  regenerated  ovary  should  be  preferred.  The  only  other  evidence  we 
have  is  that  derived  from  the  character  of  the  offspring. 


*Simple  inspection  of  the  external  genitalia  appears  to  be  sufficient  in  rabbits  to  show 
whether  or  not  the  uterus  is  functioning  normally. 


EXAMINATION   OF   OBSERVATIONS   OF   GUTHRIE   AND   MAGNUS.  15 

Since  in  Outline's  experiments  the  character  of  the  germ-cells  furnished 
by  the  mother  is  in  question,  we  may  conveniently  group  the  experiments 
according  to  the  character  of  the  male  used. 

SERIES  I.     ROOSTER  BLACK. 

Black  hen  Bl,  control,  mated  with  the  black  rooster,  had  13  black  chicks 
with  ' 'grayish-yellow  breasts  and  throats,  and  frequently  the  under  sur- 
faces of  the  tips  of  the  wings  were  light  colored  as  well,  but  the  plumage  on 
the  entire  dorsal  surface  was  always  solid  black." 

Black  hen  B  3  and  white  hen  W  3  had  their  ovaries  exchanged  and  were 
later  bred  to  "the  black  rooster."  Black  hen  B3  produced  six  black 
chicks,  four  apparently  normal,  but  two  <(  with  white  legs."  We  are  not 
told  whether  this  whiteness  was  of  down  or  final  plumage,  but  the  state- 
ment is  added:  "In  regard  to  the  chicks  from  this  hen  described  as  ordi- 
nary black,  some  doubt  exists  as  to  whether  the  ventral  light-colored  area 
described  for  normal  black  chicks  was  not  lighter  and  greater  in  extent  in 
all  cases  than  in  the  normal  chicks."  Since  this  ventral  lightness  is  of 
down  only,  not  of  later  plumage,  we  are  led  to  infer  that  the  description 
of  the  abnormal  black  chicks  was  also  based  on  the  down  colors.  And 
since,  further,  white  chicks  are  not  white  in  the  down,  but  blacks  chicks  are 
light  below  in  the  down,  it  seems  that  Guthrie's  real  meaning  is  that  the 
two  abnormal  chicks  had  light  legs  (not  white  legs)  in  the  down.  But 
this  does  not  indicate  whether  the  adult  plumage  in  that  region  was  to 
be  black  or  white.  If  this  reasoning  is  correct,  then  the  only  difference 
between  these  two  chicks  and  ordinary  black  chicks  is  that  they  perhaps 
had  more  extensive  light  ventral  areas  in  the  down  plumage,  the  light  area 
extending  onto  the  legs.  This  has  no  relation  whatever  to  the  plumage 
condition  of  the  white  race  from  which  the  graft  was  taken  and  can  not 
fairly  be  assigned  to  that  source. 

If  the  six  chicks  were  produced  from  regenerated  ovary  (z.  e. ,  from  germ- 
cells  of  the  black  hen  not  removed  at  the  operation)  we  should  expect  them 
all  to  be  black,  as  they  were.  If  they  were  produced  from  transplanted 
ovarian  tissue  without  foster-mother  influence,  we  should  expect  them  all 
to  be  white,  which  they  were  not.  For  the  white  of  Leghorn  fowls,  accord- 
ing to  Bateson  and  Davenport,  behaves  as  a  dominant  character  in  crosses 
with  black,  cross -breds  being  white  or  white  spotted  sparingly  with  black. 
Unless,  therefore,  we  grant  that  these  six  chicks  came  from  regenerated 
ovarian  tissue  of  the  black  mother  herself,  we  are  forced  to  assume  that  the 
ovarian  tissue  transplanted  from  the  white  hen  completely  changed  its  char- 
acter from  white  to  black  within  the  black  hen.  It  is  a  hypothesis  at  least 
equally  plausible  to  suppose  that  no  cells  were  changed  in  character,  but  a 
few  were  overlooked  in  the  castration. 

White  hen  W  3 ,  having  received  the  ovary  from  black  hen  B  3 ,  was  also 
mated  with  '  'the  black  rooster. ' '  She  produced  twelve  '  'white  chicks  with 
black  spots  on  the  dorsal  surface  of  the  head,  neck,  wings,  back,  or  on  the 


16         ON  GERMINAL  TRANSPLANTATION  IN  VERTEBRATES. 

tail."  This  is  such  a  result  as  we  should  expect  had  the  hen  not  been  oper- 
ated upon  at  all.  It  is  fully  accounted  for  if  we  assume  that  the  ova  which 
produced  these  twelve  chicks  came  from  regenerated  ovarian  tissue  of  the 
white  mother  herself.  On  the  other  hand,  if  the  transplanted  ovary  had 
produced  the  chicks  without  any  foster-mother  influence,  the  chicks  should 
have  been  all  black  with  light  ventral  surfaces,  which  they  were  not.  Again 
the  regeneration  hypothesis  presents  far  less  difficulty  than  that  of  a  suc- 
cessful transplantation. 

SERIES  II.     ROOSTER  WHITE, 

White  hen  W 1  control,  mated  with  the  wljite  rooster,  had  eighteen  chicks 
"pure  white  to  light  buff  when  hatched."  White  hen  W2  and  black  hen 
B  2  had  their  ovaries  exchanged,  and  were  later  bred  to  the  white  rooster. 

Black  hen  B  2  produced  nine  white  chicks  and  11  white  spotted  sparingly 
with  black.  Such  a  result  as  this  is  the  usual  consequence  of  a  cross 
between  black  fowls  and  white  ones;  that  is,  it  is  what  might  have  been 
expected  had  the  black  hen  never  been  operated  upon.  And,  on  the  other 
hand,  if  the  functional  ova  came  from  the  transplanted  ovary,  the  expectation 
would  not  be  materially  different,  though  the  breeding  capacity  of  the  young 
would  be  different  in  the  two  cases.  Unfortunately  this  was  not  tested. 

The  white  hen  W2,  which  had  received  the  black  ovary  from  B  2,  pro- 
duced five  chicks.  Three  were  white,  one  white  spotted  with  black,  and 
one  black.  A  white  hen  not  operated  upon  might  be  capable  of  producing 
all  three  sorts  when  mated  with  a  white  rooster  of  a  similar  character; 
that  is,  both  parents  might  be  Mendelian  heterozygotes  bearing  black  as 
a  recessive  character,  in  which  case  one-quarter  of  the  young  should  be 
black.  Now,  the  numerical  result  is  not  at  variance  with  such  an  interpre- 
tation. But  if  the  same  white  rooster  was  used  in  this  mating  as  with  B  2, 
it  is  surprising  that  no  black  young  were  produced  by  B  2 .  Guthrie  does 
not  expressly  state  that  the  same  rooster  was  used  in  both  cases,  but  we 
assume  this  to  have  been  the  case  from  his  use  of  the  expression  '  'the  white 
rooster. ' '  If  different  males  were  used  in  the  two  cases,  one  may  well  have 
been  homozygous,  the  other  heterozygous.  In  that  case  the  black  chick 
as  well  as  the  white  and  the  spotted  ones  may  have  come  from  regenerated, 
not  from  transplanted  tissue.  But  if  the  same  white  rooster  was  used  in 
both  cases,  it  is  still  equally  difficult  to  account  for  the  black  chick  as  a 
product  of  a  transplanted  germ-cell  or  of  regenerated  ovarian  tissue  of  the 
white  mother.  For  unless  the  white  male  was  heterozygous  in  black  we 
should  expect  no  black  young  to  be  produced  even  were  every  egg  which  he 
fertilized  produced  by  a  pure-black  hen,  instead  of  by  a  white  hen  possibly 
carrying  borrowed  black  germ-cells. 

Control  matings  of  the  white  rooster  with  normal  black  hens,  or  of  the 
black  chick  when  it  became  adult,  would  have  cleared  up  the  case,  but  no 
control  crosses  were  made  by  Guthrie.  The  control  mating  of  "the  white 
rooster' '  with  a  normal  white  hen  W 1  was  not  a  sufficient  control  of  his 


EXAMINATION   OF  OBSERVATIONS   OF   GUTHRIE  AND   MAGNUS.  17 

breeding-  capacity.  It  does  not  prove  him  to  have  been  homozygous  in 
white.  If  W 1  was  homozygous,  only  white  chicks  would  be  expected,  what- 
ever the  character  of  the  white  rooster. 

We  have  now  examined  in  detail  the  two  pairs  of  transplantation  exper- 
iments which  form  the  entire  basis  of  Guthrie 'e  assumption  that  the  foster- 
mother  may  in  a  case  of  homoplastic  transplantation  affect  the  character  of 
the  offspring.  In  no  one  of  the  four  cases  does  the  hypothesis  that  the 
transplanted  ovary  functioned  offer  less  difficulty  than  the  hypothesis  that 
only  regenerated  ovarian  tissue  functioned.  In  two  of  the  four  cases  the 
advantage  is  overwhelmingly  with  the  latter  hypothesis.  That  ovarian 
tissue  might  easily  be  left  behind  in  exchanging-  ovaries  between  two  ani- 
mals Guthrie  frankly  admits  in  a  recent  paper  (1910),  citing  experiences 
of  his  own  to  show  just  how  this  might  come  about.  He  still  maintains, 
however,  his  belief  in  foster-mother  influence,  because,  we  believe,  of  a  fail- 
ure to  grasp  fully  the  laws  of  inheritance  of  the  character  which  he  used  as 
a  criterion.  A  similar  failure  is  shown  by  the  comment  which  he  makes 
in  Science  (1909)  upon  the  case  which  we  have  more  fully  described  in  this 
paper  (Group  I) .  Referring  to  our  failure  to  detect  foster-mother  influence 
in  the  young  borne  by  female  27,  he  says  :  "Had  the  operated  pig  been 
bred  to  a  male  of  the  same  strain  as  the  pig  from  which  the  engrafted  ovary 
was  obtained  *  *  *  characteristics  in  the  offspring-  indicative  of  such 
influence  might  have  been  obtained."  Now,  suppose  the  operated  pig  had 
been  so  bred,  what  result  might  have  been  expected?  Exactly  that  which 
was  obtained  from  the  mating  with  an  albino,  only  we  should  have  been  left 
in  uncertainty,  precisely  as  in  Guthrie 's  own  experiments,  as  to  whether 
the  pigmentation  of  the  offspring  was  due  to  maternal  or  paternal  influence . 
By  the  mating  with  an  albino  male  all  such  uncertainty  was  eliminated, 
since  it  was  rendered  sure  that  if  the  offspring-  were  pigmented  they  could 
have  derived  this  character  from  no  other  source  than  the  transplanted 
ovary  of  the  little  black  g^iinea-pig. 

Our  case  does  not  prove  that  foster-mother  influence  is  impossible.  No 
such  claim  is  made  for  it.  But  our  observations  do  show  that  evidence  such 
as  Guthrie  has  presented  is  wholly  without  value  in  establishing-  foster- 
mother  influence,  and  that  in  one  specific  case,  the  first  critical  case  on  rec- 
ord, we  believe,  no  foster-mother  influence  is  detectable. 

In  view  of  our  own  experiments  on  gfuinea-pigs,  in  which  the  source  of 
the  tissue  which  liberated  the  ova  is  fully  established  and  in  which  no  foster- 
mother  influence  is  detectable,  we  may  fairly  ask  that  the  experiments  with 
fowls  be  repeated  on  adequately  controlled  material  before  we  accept  the 
interpretation  which  Guthrie  has  given  to  his  results.* 

*While  this  paper  was  in  press  our  attention  was  called  to  the  fact  that  Dr.  C.  B. 
Davenport  (1910,  Proc.  Soc.  Exp.  Biol.  Med.,vol.  vn,  p.  168)  had  indeed  repeated  Guth- 
rie's  experiment  with  fowls,  on  material  adequately  controlled  and  of  known  pedigree. 
The  result  was  that  in  every  case  castration  was  incomplete  and  ovarian  regeneration 
occurred,  leading  to  the  production  of  young  showing  no  influence  of  the  introduced 
graft. 


18         ON  GERMINAL  TRANSPLANTATION  IN  VERTEBRATES. 

The  work  of  Magnus  demands  no  extended  discussion.  Into  a  black 
rabbit  were  introduced  the  ovaries  of  a  white  one.  The  grafted  black  rabbit 
was  then  mated  with  a  white  male  rabbit.  Two  litters  of  young  resulted 
which  consisted  in  part  of  black  animals  and  in  part  of  white  ones.  There 
is  no  question  of  an  intermediate  or  modified  character  in  the  young,  such  as 
Guthrie  would  have  us  believe  occurred  in  his  experiments.  If  any  foster- 
mother  influence  was  exerted  at  all,  it  was  such  as  changed  the  character 
of  germ-cells  completely  from  the  albino  to  the  fully  pigmented  condition. 
But  this  supposed  influence  manifested  itself  in  part  only  of  the  germ-cells 
subjected  to  the  new  somatic  environment;  the  others  were  unaffected. 

An  alternative  interpretation  is  plainly  possible.  The  ovary  observed 
at  the  autopsy  of  the  grafted  black  rabbit  may  have  been  regenerated  from 
fragments  of  ovarian  tissue  not  removed  by  castration.  We  do  not  under- 
stand that  there  was  anything  in  the  observed  position  of  the  organ  decisive 
either  for  or  against  such  an  interpretation. 

It  is  known  from  studies  of  Hurst  and  of  Castle  that  the  albino  condition 
in  rabbits  is  a  Mendelian  recessive  to  black.  The  grafted  black  rabbit  may 
have  been  a  heterozygous  black,  containing  albinism  as  a  recessive  char- 
acter. In  that  case,  if  the  black  rabbit  had  not  been  operated  upon,  but  had 
been  mated  with  an  albino  male,  we  should  have  expected  that  young  would 
be  produced  half  of  which  were  black,  half  albinos.  This  is  substantially 
the  result  observed.  Accordingly,  so  far  as  the  character  of  the  young  is 
concerned,  there  is  no  reason  to  think  that  they  were  produced  from  intro- 
duced ovarian  tissue  rather  than  from  regenerated  ovarian  tissue  of  the 
black  rabbit  herself. 

But  if  we  adopt  the  interpretation  that  the  observed  ovary  was  really  an 
introduced  ovary,  we  encounter  this  difficulty.  If  introduced  egg-cells 
through  somatic  influences  were  changed  in  character  so  that  they  produced 
black  young  instead  of  white  ones,  why  were  not  all  the  egg-cells  so  affected? 
Were  they  not  all  subject  to  the  same  somatic  influences?  On  the  whole, 
therefore,  we  meet  fewer  difficulties  by  interpreting  the  observed  ovary  as 
a  regenerated  ovary  rather  than  as  a  transplanted  ovary. 

6.  A  REVIEW  OF  THE  LITERATURE  ON  GRAFTING   OF  TESTICLES. 

The  work  on  testicle  grafting  is  less  voluminous  than  that  on  ovarian 
grafting.  In  a  general  way  some  of  the  more  uncritical  of  the  early  inves- 
tigators reported  results  of  a  positive  nature;  but  later  work  along  the  same 
lines  gives  results  of  an  entirely  different  character. 

Berthold  in  1849  interchanged  testicles  between  two  cocks  after  castrating 
both  animals.  The  organs,  one  in  each  animal,  were  not  sutured.  Five 
months  later  they  were  found  grown  against  the  colon  in  both  cases,  and 
full  of  active  spermatozoa.  The  cocks  retained  their  sexual  instincts. 

Mantigazza  (i860),  experimenting  on  frogs,  found  living  testicular  tissue 
in  grafted  animals  after  a  period  of  70  days.  He  thought  that  the  tissue 
preserved  its  structure.  Bizzozero  (1868)  confirmed  these  results. 


GRAFTING   OF  TESTICLES.  19 

Cheveau  (1890)  in  a  brief  note  described  autoplastic  testicular  transplan- 
tation, apparently  of  adult  tissue,  in  sheep.  He  obtained  nourishment  of 
the  exterior  of  the  testicle,  but  concludes  that  the  operation  is  futile  if  the 
testicle  is  really  detached  from  its  own  blood-supply. 

A.  Lode  (1891)  reported  the  results  of  experiments  on  cocks  which  were 
castrated,  their  organs  being- transplanted  into  subcutaneous  connective  tis- 
sue. One  cock  eight  months  after  operation  revealed  a  tumor  of  bean  size 
under  the  skin.  This  appeared  vascularized  and  contained  living  sper- 
matozoa. Another  cock,  in  which,  after  being  caponized  by  a  professional 
caponizer,  the  testicles  were  thrown  back  into  the  body  cavity,  showed  a 
bean-sized  testis  attached  to  the  peritoneum  at  the  site  of  the  old  wound, 
containing  living  spermatozoa.  There  were  also  numerous  spermatozoa 
contained  in  little  testicles  in  various  parts  of  the  body  cavity,  which  were 
regenerated  bits  of  the  testicles,  crushed  in  the  process  of  caponizing.  He 
states  that  he  always  found  testes  remaining  in  capons,  no  matter  how  care- 
fully castrated.  This  work  therefore  would  allow  one  to  make  a  somewhat 
different  interpretation  of  Berthold's  work  than  he  himself  made:  the  sup- 
posedly transplanted  testicles  may  have  been  regenerated  from  fragments 
never  removed. 

Hanau  (1897),  also  working  on  fowls,  found  difficulty  in  completely  cas- 
trating cocks,  and  showed  that  a  small  amount  of  the  testicle,  if  left  behind, 
forms  little  capsules,  containing  sperm  and  embedded  in  connective  tissue. 
Testicles  transplanted  into  hens  were  encapsulated  and  resorbed. 

In  1898  Goebell,  questioning  the  results  of  Berthold,  operated  on  guinea- 
pigs  and  found  that  transplanted  testes  in  the  body-cavity  became  necrotic 
after  two  days,  except  the  most  superficial  layers,  which  showed  mitoses. 

Herlitzka  (1899),  in  a  very  critical  paper,  reports  the  results  of  the  trans- 
plantation of  testicles  in  tritons.  In  all,  32  animals  were  used,  20  females 
and  12  males.  These  experiments  were  in  part  planned  to  test  the  theory 
of  Ribbert  (1898),  who,  working  on  a  large  series  of  rabbits,  found  degener- 
ation to  take  place,  or  more  correctly  a  process  of  regression  to  a  more 
primitive  type  of  cell,  both  when  bits  of  tissue  were  placed  in  lymph  nod- 
ules and  when  whole  testicles,  autoplastic  or  homoplastic,  were  fixed  by  a 
peritoneal  suture.  Ribbert  found  that  the  epithelium  of  the  efferent  canals 
resisted  longer  than  the  epithelium  with  specific  function.  He  concluded 
that  transplantation  of  the  testicles  was  not  possible  because  there  is  con- 
cerned a  gland  which  discharges  its  secretion  externally. 

To  test  this  last  theory  Herlitzka  used  tritons  both  in  winter  stages  and  in 
summer  stages .  The  testicles  were  transferred  from  one  animal  to  another, 
and  also  to  females  ;  and  in  some  males  one  of  the  animal's  own  testicles 
was  left  as  a  control.  His  results  in  brief  were  degeneration  of  the  trans- 
planted tissue  under  all  conditions  in  from  ten  to  fifty-two  days,  usually 
about  a  month.  The  state  of  the  testicle,  whether  resting  or  active,  made 


20         ON  GERMINAL  TRANSPLANTATION  IN  VERTEBRATES. 

no  difference.  The  efferent  parts  of  the  tubules  degenerated,  though  more 
slowly  than  the  sperm-forming  parts.  The  author  is  inclined  to  attribute 
non-success,  in  part  at  least,  to  the  absence  of  trophic  stimulation  of  the 
nervous  system,  though  he  admits  his  view  is  far  from  being  proved. 

Zalachas  in  1907  gives  the  result  of  autoplastic  transplantation  in  frogs, 
in  which  he  found  living  sperm  preserved  after  one  month.  He  does  not 
claim  that  this  proves  activity  of  the  transplanted  gland,  for  as  a  control 
he  found  (completely  degenerated  but  containing  active  spermatozoa)  a 
testicle  which  had  been  for  one  month  in  a  sterile  tube.  Zalachas  also 
transplanted  testicles  of  very  young  dogs  into  older  dogs,  and  in  seven 
cases  got  almost  complete  degeneration  at  the  end  of  one  month. 

Foges  (1898)  extended  the  result  of  Lode's  work  on  caponizing  cocks, 
without  obtaining  any  very  convincing  results. 

Fo£  (1901),  in  a  very  able  paper,  sums  up  the  results  of  others,  and  then 
describes  in  detail  his  own  work  on  dogs,  autoplastic  and  homoplastic,  which 
gave  negative  grafts  after  one  month.  The  organs  of  three-day  old  dogs 
were  used  for  the  transfer.  In  another  experiment  a  part  of  one  of  these 
testicles  was  carefully  sutured  by  the  tissues  to  another  testicle,  in  which, 
though  left  in  situ,  a  part  of  one  end  had  been  cut  off.  The  cut  faces  of 
the  two  testicles  were  thus  brought  face  to  face.  Complete  degeneration 
took  place  both  in  the  graft  and  in  the  remaining  portion  of  the  animal's 
own  testicle. 

Foa  therefore  combats  the  theory  of  the  lack  of  efferent  ducts  suggested 
by  Ribbert.  His  results  are  the  same  whether  the  testicle  is  embryonic  or 
adult,  whether  whole  organs  or  parts  of  organs  are  used.  Foa  gives  weight 
to  traumatism,  brought  about  by  the  operator,  as  the  essential  cause  of 
degeneration. 

We  believe  that  the  results  of  Maximow  (1899),  in  the  study  of  the  regen- 
erative capacity  of  the  testicle  after  artificial  wounds,  show  the  testicular 
tissue  to  be  of  a  very  delicate  nature,  easily  unbalanced  b>  slight  mechan- 
ical disturbances.  The  work  of  Cevolotto  (1909)  goes  far  towards  strength- 
ening this  view.  This  author  made  a  careful  study  of  the  cell  changes  in 
autoplastic  transplantation  of  bits  of  testicular  tissue  into  the  tissue  of  the 
ear.  His  results,  in  a  word,  show  the  harmful  influence  to  the  highly 
differentiated  epithelial  tissue,  which  last  is  quickly  converted  into  embry- 
onic tissue.  Sertoli  cells  increase  and  epithelial  giant  cells  appear. 

With  this  idea  in  mind  the  results  of  Guthrie  (1910)  are  indeed  surpris- 
ing, though  it  must  be  confessed  that  a  review  of  the  literature  shows  the 
cock  to  be  a  very  likely  subject  for  transplantation  experiments.  Guthrie 
reports  normal  testicular  structure  existing  in  grafts  after  four  months. 
He  hopes  to  produce  artificial  fertilization  in  hens  from  such  testicular 
grafts  in  continuation  of  his  experiments  on  the  effect  of  the  foster-soma 
on  engrafted  germ-cells. 


GRAFTING  OF   TESTICLES.  21 

r.  NEW  .OBSERVATIONS  ON  GRAFTING  OF  TESTICLES. 

In  order  thoroughly  to  satisfy  ourselves  whether  germinal  transplantation 
is  possible  when  tissue  of  the  male  sexual  gland  is  used  as  a  graft,  the 
following  experiments  were  performed  on  rats  before  ovarian  work  was 
started.  The  operations  were  homoplastic  and  the  technique  simple.  The 
animals  used  to  supply  the  graft  were  new-born  males  or  those  only  a  few 
days  old,  while  those  into  which  the  tissue  was  grafted  were  young  adults 
of  the  same  sex.  No  attempt  was  made  to  unite  the  efferent  ducts,  or  to 
supply  special  arterial  contact,  the  young  testicle  being  simply  dropped 
into  the  tunica  vaginalis  after  its  original  contents  had  been  carefully 
removed. 

The  rat  was  etherized,  the  scrotum  sterilized  and  opened  at  its  discal 
end  by  a  small  incision.  The  testicle  was  then  drawn  out,  the  tunic  split, 
and  the  entire  contents  removed,  leaving  the  end  of  the  spermatic  artery 
free.  The  other  testicle,  now  quickly  removed  from  the  young  animal  sup- 
plying the  graft,  was  carefully  manipulated  and  placed  within  this  tunica, 
sometimes  with  its  own  envelope  intact  and  sometimes  with  one  of  its 
ends  cut  across.  The  tunica,  now  containing  the  young  grafted  testicle, 
was  closed  by  fine  silk  sutures,  the  testicle  replaced,  and  the  scrotal  wound 
also  closed.  There  was  considerable  extravasation  of  blood  from  the  sper- 
matic artery  in  a  few  cases,  distending  the  tunic  and  sometimes  leaking 
through  the  sutures.  The  testicle  of  the  other  side  was  removed  through 
a  small  incision  in  the  scrotum  and  discarded,  a  suture  being  placed  around 
its  spermatic  cord. 

Thirty-three  rats  were  thus  operated  upon.  One  died  six  days  after  the 
operation;  the  rest  were  killed  at  periods  of  from  one  month  to  two  months 
after  the  operation.  Four  of  them  showed  small  abscesses  in  the  operative 
region.  The  other  twenty-eight  gave  no  evidences  of  ever  having  been 
infected.  In  general,  the  appearance  was  very  uniform.  The  epididymis 
was  flabby,  and  in  the  region  of  the  graft  there  was  either  a  very  small 
yellowish  body  or  nothing  but  a  bit  of  connective  tissue  surrounding  the 
old  stitches  of  the  tunica.  A  number  of  the  specimens  were  saved,  but 
only  one  was  considered  to  be  promising  enough  to  warrant  sectioning. 
The  microscopic  examination  was  entirely  negative  so  far  as  showing  the 
presence  of  living  testicular  tissue  was  concerned,  and  so  the  experiments 
were  discontinued. 

It  is  evident  from  our  experience,  as  from  that  of  others,  that  testicular 
tissue  is  much  more  sensitive  to  injury,  mechanical  or  otherwise,  than  is 
ovarian  tissue. 


22  ON  GERMINAL  TRANSPLANTATION  IN  VERTEBRATES. 

r.  BIBLIOGRAPHY  OF  OVARIAN  GRAFTING. 

ARENDT,  E. 

1898.  Ovarientransplantationen.    Verhandl.  d.  Gesellsch.  deutsch.  Naturf.  u.  Aerzte, 

Leipz.,  v.  70,  pt.  2:  173.    Also,  Centralbl.  f.  Gynak.,  Leipz.,  v.  22  :  1116. 
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deutsch.  Naturf o rsch.  u.  Aerzte,  Leipz.,  v.  77,  pt.  2:  231. 

BASSO,  G.  L.    1905.  Ueber  Ovarientransplantation.     Arch.  f.  Gynak.,  Berl.,  v.  77:  51-62. 
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BURCKHARD,  G. 

1908.  Ueber  Ovarientransplantation.    Berl.  klin.  Woch.,  v.  45:  1337. 

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Empire,  Lond.,  v.  11 :  215-223. 
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1900.  Also,  Post-graduate,  N.  Y.,  v.  15:  546-548. 

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1901.  Also,  Jour.  Amer.  med.  assoc.,  Chicago,  v.  27:  357-360. 

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379-385. 
FoA,  C. 

1900.  La  greffe  des  ovaires,  en  relation  avec  quelques  questions  de  biologic  ge'ne'rale. 

Arch.  ital.  de  biol.,  Turin,  v.  34 :  43-75. 

L'innesto  delle  ovaia  in  rapporto  con  alcune  questioni  di  biologia  generale. 
Riv.  di  sc.  biol.,  Turin,  v.  2:  436-462. 

1901.  SulP  innesto  delle  ovaie.     Riv.  di  biol.  gen.,  Turin,  v.  3  :  321-328. 
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Also  (Transl.),   Arch.  ital.  de  biol.,  Turin,  v.  35:  364-372. 
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1897.  [On  the  transplantation  of  ovaries.]     St.  Petersburg,  1897,  45  pp.,  8°.     (Rus- 
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Die  Schwangerschaft  bei  der  Transplantation  der  Eierstocke.     Centralbl.  f. 
Gynak.,  Leipz.,  v.  21 :  663-668. 


BIBLIOGRAPHY.  23 

GUTHRIE,  C.  C. 

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Jour.  Amer.  med.  assoc.,  Chicago,  v.  51:  1314. 
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1907.  Also,  Proc.  Amer.  physiol.  soc.,  Boston,  1907:  p.  xvi. 
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1901.  Ovarium  und  Menstruation.  Verhandl.  d.  deutsch.  Gesellsch.  f.  Gynak.,  Leipz., 

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Also,  Sitzungsb.  d.  k.  Akad.  d.  Wissenschaft.  Math.-naturw.  CL,  Wien,  v. 

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1899.  Ueber  Ovarientransplantation.    Wien.  klin.  Wochenschr.,  v.  12 :  1243. 
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1890.  Preliminary  note  on  the  transplantation  and  growth  of  mammalian  ova  within 
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1897.  Further  note  on  the  transplantation  and  growth  of  mammalian  ova  within  a 

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1900.  Einiges  tiber  Ovarientransplantation.    Biol.  Centralbl.,  Leipz.,  v.  20:  619-624. 
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Also  (Abstr.),  Arch.  ital.  di  ginec.,  Naples,  v.  3:  134-137. 
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1896.  Einige  Versuche  iiber  Ovarientransplantation  bei  Kaninchen.    Centralbl.  f. 

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1897.  Bemerkungen  zu  der  Mittheilung  des  Herrn  Dr.  Woldemar  Grigorieff  "  Die 

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1898.  Zur  Ovarientransplantation.  (Geburt  am  normalen  Ende  der  Schwangerschaft 

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Zu  Dr.  Arendt's  Demonstration  und  Bemerkungen  zur  Ovarientransplantation 
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1899.  Ueber  Ovarientransplantation.     Wien.  klin.  Wochenschr.,  v.  12:  1219-1222, 

1243-1244. 

1900.  Die  Ovarientransplantation ;  experimentclle  Studie.    Arch,  f .  Gynak.,  Berl., 

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LIMON,  .    1904.    Note  sur  la  transplantation  de  1'ovaire.    Compt.  rend.  Soc.  de 

biol.,  Paris,  v.  57:  143-145. 


24         ON  GERMINAL  TRANSPLANTATION  IN  VERTEBRATES. 

LIMON,  .    1904.  Observations  sur  1'dtat  de  la  glande  interstitielle  dans  les  ovaires 

transplants,  Jour,  de  physiol.  et  depath.  gen.,  Paris,  v.  6:  864-874. 
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greffe  ovarienne  he'teroplastique ;  grossesse  et  accouchement  d'un  enfant 

vivant;  grossesse  apres  ablation  des  deux  ovaires.    Jour.  d.  sages-femmes, 

Paris,  v.  35 :  290. 
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soc.  of  the  State  of  Calif.,  Monterey,  v.  2:9  259-268.  Also,  Amer.  jour.obst, 

N.  Y.,  v.  40:   214-218. 
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MARCHESE,  B. 

1898.  Sulla  trapiantazione  delle  ovaie.    Arch.  ital.  di  ginec.,  Naples,  v.  1 :  340-363. 

1899.  Also  (Abstr.  in  German],  Centralbl.  f.  Gynak.,  Leipz.,  v.  23:  951. 
MARSHALL,  F.  H.  A.,  and  JOLLY,  W.  A. 

1906.  Preliminary  communication  upon  ovarian  transplantation  and  its  effect  on  the 

uterus.     Proc.  Physiol.  soc.,  Lond.,  1906  :  p.  xxvi. 

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1908.  On  the  results  of  heteroplastic  ovarian  transplantation  as  compared  with  those 

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MAUCLAIRE,  P. 

1900.  Autogreffes  sous-cutane'es  des  ovaires  apres   salpingo-ovariectomie,  Cong,  in- 

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1908.  Les  greffes  ovariennes  avec  ou  sous  anastomoses  vasculaires  chez  la   femme. 

Arch,  gdn  de  chir.,  Paris,  v.  2 :  571-585. 

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179-191. 

MAXIMO,  A.  1900.  Die  histologischen  Vorgange  bei  der  Heilung  von  Eierstocks-Ver- 
letzungen  und  die  Regenerations  -  Fahigdes  Eierstocksgewebes.  Virch. 
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MONPROFIT,  A.    1901.  Greffe  de  1'ovaire.     Arch.  prov.  de  chir.,  Paris,  v.  10:  129-142. 
MORRIS,  R.  T. 

1895.  The  ovarian  graft.    N.  Y.  med.  jour.,  1895,  v.  62:  436-437. 

Ovarian  transplantation.    (In  his  Lectures  on  appendicitis,  pp.  156-159.  New 
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1901.  Notes  on  ovarian  grafting.    Med.  rec..  N.  Y.,  v.  59:  83-87. 

1902.  Ovarian  transplantation.    South.  Calif,  pract,  Los  Angeles,  v.  17:  175-176. 

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PANKOW,  1907.  Ueber  Reimplantation  der  Ovarien  beim  Menschen.    Beitr.  z. 

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BIBLIOGRAPHY,  i 


25 


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8.  BIBLIOGRAPHY  OF  GRAFTING  OF  TESTICLES. 

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26      **  %  :  '•"  vCto  KR^N^^TRA^NSPLANTATION  IN  VERTEBRATES. 

MAXIMOW,   ALEXANDER.     1899.  Die  histologischen  Vorgange  bei  der  Heilung  von 

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